The present invention relates to a new compound comprising the reaction product of guaran and 5,5-deiphenyl-2,4-imidazolidinedione (phenytoin).
Phenytoin, commonly known as dilantin, is 5,5-phenyl-2,4-imidazolidinedione and is a well known therapeutic agent useful as an anti-convulsant effective for the treatment of generalized tonic-clonic seizures ("grand mal") in adults and children, and is also useful in the treatment of simple and complex partial seizures ("focal" and "tempral lobe and psychomotor").
5,5-diphenyl-2,4-imidazolidinedione and methods for its production are described in U.S. Pat. No. 2,409,754. The pharmacology of phenytoin in Anticonvulsants, Vida, Julius A. Ed. 176-284, Academic Press, New York, 1977.
Phenytoin or 5,5-dipenyl-2,4imidazolidinedione, is practically insoluble in water and is soluble in alcohol to the extent that one gram dissolves in about 60 ml of absolute alcohol. Numerous attempts have been made to dissolve or otherwise suspend 5,5-diphenyl-2,4-imidazolidinedione in water and other common pharmaceutically acceptable carriers; however, because of the hydrophobicity of this compound (phenytoin) none has provided sufficient reduction in particle size to allow the absorption of phenytoin, or sufficiently homogeneous suspension to allow for uniformity of dosage. In addition, not only must this compound be absorbed but it must be absorbed in such a way as to produce predictable and sustainable blood levels.
For example, the use of commonly employed high molecular weight suspending agents, which depend on viscosity to suspend the hydrophobic particles of phenytoin, result in suspensions which do not suspend since the phenytoin remains in the crystalline form and floats on the surface of such suspensions. Phenytoin is hydrophobic because of the strong intermolecular bonding of the phenytoin molecules one to the other, resulting in a crystal lattice structure that has a melting point of 295.degree.-298.degree. C. The phenytoin crystal structure is such that bonding between molecules creates a rigid polymer. Phenytoin is capable of bonding to cellulose polymers through electrostatic interaction, however such complexes do not allow the release of the phenytoin as they travel through the gastrointestinal tract. Since the polymer is not degraded into smaller units within the gastrointestinal tract, the phenytoin would remain with the polymer. In order for absorption to occur from such a polymer, the polymer must be subdivided to units which combined with the phenytoin must not exceed a molecular weight of 700-900. Cellulose polymers have molecular weights ranging in the hundred of thousands, and are not degraded in the gastrointestinal tract.
To date, there has been no satisfactory solution of the problem of forming a suitable pharmaceutically acceptable preparation of phenytoin which is easily administered yet capable of allowing the transport of phenytoin across the intestinal mucosa.
It is an object of the present invention to provide an easily suspended compound, one which results from the molecular interaction of phenytoin with a hydrophillic macromolecule which is degradable within the gastrointestinal tract. This resultant new macromolecular species bearing the active phenytoin component with it, may then be administered in a dosage form to animals and humans which results in the absorption of phenytoin at a therapeutically desireable rate and allows for the sustenance of therapeutic blood levels, while minimizing the possibility of toxic events.